Low density lipoprotein natural history, prognosis and complications

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Rim Halaby, M.D. [2]

Overview

  • There is a direct association between cardiovascular death and duration of elevated plasma LDL-cholesterol (LDL-C) levels. In most cases, elevated LDL is a contribution of both polygenic factors and environmental influences.[1]
  • According to Qebec Cardiovascular study in 2001 increased density, and reduced size < 25.6 nm carry significant unfavorable clinical implications. However, LDL diameter remains a controversial predictor of outcome based on conflicting data in the literature.[2]
  • Stampfer and colleagues (1996) also revealed in a nested case-control study that elevated triglyceride component within LDL has independent association with myocardial infarction (MI). Clinically, the study revealed that non-fasting triglyceride levels is an independent predictor of MI, especially when combined with elevation of total cholesterol.
  • However, the occurrence of isolated small dense LDL phenotype is quite uncommon. It is usually part of multiple metabolic disturbances, including low HDL, elevated triglyceride levels, increased waist-to-hip ratio, and insulin resistance.
  • The decreased affinity of small dense LDL particles for LDL receptors has been postulated to be the cause of atherogenic properties of small dense LDL. They are more prone to oxidation,[3] have higher affinity to vascular proteoglycans,[4] and are preferentially taken up by macrophages via scanvenger proteins that promote atherosclerosis.[5]

References

  1. Rader DJ, Cohen J, Hobbs HH (2003). "Monogenic hypercholesterolemia: new insights in pathogenesis and treatment". J Clin Invest. 111 (12): 1795–803. doi:10.1172/JCI18925. PMC 161432. PMID 12813012.
  2. Lamarche B, St-Pierre AC, Ruel IL, Cantin B, Dagenais GR, Després JP (2001). "A prospective, population-based study of low density lipoprotein particle size as a risk factor for ischemic heart disease in men". Can J Cardiol. 17 (8): 859–65. PMID 11521128.
  3. Tribble DL, Holl LG, Wood PD, Krauss RM (1992). "Variations in oxidative susceptibility among six low density lipoprotein subfractions of differing density and particle size". Atherosclerosis. 93 (3): 189–99. PMID 1590824.
  4. Chapman MJ, Guérin M, Bruckert E (1998). "Atherogenic, dense low-density lipoproteins. Pathophysiology and new therapeutic approaches". Eur Heart J. 19 Suppl A: A24–30. PMID 9519339.
  5. Vergès B (2005). "New insight into the pathophysiology of lipid abnormalities in type 2 diabetes". Diabetes Metab. 31 (5): 429–39. PMID 16357786.



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